Ibogaminalog (developmental code name DM-506) is a non-selective and non-psychedelic serotonin receptor modulator of the ibogalog group related to the iboga alkaloid ibogamine but with a simplified chemical structure. It was first described in the 1960s but was subsequently further studied and reported on in the 2020s.[1][2][3][4][5][6]

Pharmacology

Ibogaminalog is known to act as an agonist of serotonin receptors, including of the serotonin 5-HT2A receptor (Ki = 17–11,190 nM; EC50Tooltip half-maximal effective concentration = 2.9–34 nM; EmaxTooltip maximal efficacy = 33–76%), the serotonin 5-HT2B receptor (Ki = 16.5–63,780 nM; EC50 = 2.9–33 nM; Emax = 68–69%), and the serotonin 5-HT6 receptor (EC50 = 2.9 nM; Emax = 96%), and as an inverse agonist of the serotonin 5-HT7 receptor (ImaxTooltip maximal inhibition = 14%).[4][3][7][8]

It is a weak to very weak monoamine reuptake inhibitor, including of serotonin, norepinephrine, and dopamine (IC50Tooltip half-maximal inhibitory concentration = 3,100 nM, 9,500 nM, and 70,000 nM, respectively), whereas it is not a significant monoamine oxidase inhibitor (MAOI) of MAO-A or MAO-B.[7] The drug also acts weakly as a negative allosteric modulator of the α7 and α9α10 nicotinic acetylcholine receptors.[2]

Ibogaminalog does not produce the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and hence may be non-hallucinogenic in humans.[4] On the other hand, it has been found to produce sedative, antidepressant-like, anxiolytic-like, antiaddictive-like, and analgesic-like effects in rodents.[4][7][5][3]

See also

References

  1. ↑ US 3529062, Renner U, "Indole derivatives as antitussive agents.", issued 15 September 1970, assigned to Novartis Corp.
  2. 1 2
  3. 1 2 3 4 Arias HR, Rudin D, Hines DJ, Contreras A, Gulsevin A, Manetti D, et al. (March 2024). "The novel non-hallucinogenic compound DM506 (3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole) induces sedative- and anxiolytic-like activity in mice by a mechanism involving 5-HT2A receptor activation". European Journal of Pharmacology. 966 176329. doi:10.1016/j.ejphar.2024.176329. hdl:2158/1354752. PMID 38253116.
  4. 1 2 Looschen K, Khatri SN, Maulik M, Salisbury C, Carman AF, Corriveau K, et al. (June 2024). "Novel psychoplastogen DM506 reduces cue-induced heroin-seeking and inhibits tonic GABA currents in the Prelimbic Cortex". Neurochemistry International. 178 105785. doi:10.1016/j.neuint.2024.105785. hdl:2158/1371513. PMID 38838988.
  5. ↑ Tae HS, Ortells MO, Tekarli BJ, Manetti D, Romanelli MN, McIntosh JM, et al. (July 2023). "DM506 (3-Methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole fumarate), a Novel Derivative of Ibogamine, Inhibits α7 and α9α10 Nicotinic Acetylcholine Receptors by Different Allosteric Mechanisms". ACS Chemical Neuroscience. 14 (14): 2537–2547. doi:10.1021/acschemneuro.3c00212. PMID 37386821.
  6. 1 2 3 Arias HR, Rudin D, Luethi D, Valenta J, Leśniak A, Czartoryska Z, Olejarz-Maciej A, Doroz-Płonka A, Manetti D, De Deurwaerdère P, Romanelli MN, Handzlik J, Liechti ME, Chagraoui A (January 2025). "The psychoplastogens ibogaminalog and ibogainalog induce antidepressant-like activity in naïve and depressed mice by mechanisms involving 5-HT2A receptor activation and serotonergic transmission". Prog Neuropsychopharmacol Biol Psychiatry. 136 111217. doi:10.1016/j.pnpbp.2024.111217. PMID 39662723.
  7. ↑ Arias HR, Micheli L, Jensen AA, Galant S, Vandermoere F, Venturi D, Manetti D, Romanelli MN, Ghelardini C, Marin P, Di Cesare Mannelli L (March 2025). "Ibogalogs decrease neuropathic pain in mice through a mechanism involving crosstalk between 5-HT2A and mGlu2 receptors". Biomed Pharmacother. 184 117887. doi:10.1016/j.biopha.2025.117887. hdl:2158/1423286. PMID 39938347.
source: https://en.wikipedia.org/wiki/Ibogaminalog